Data from: Evolutionary dynamics of hepatitis C virus in patients with mixed infection over a 13-year follow-up period

High throughput sequencing enables large-scale studies of evolution within rapidly evolving hepatitis C virus populations. Sequencing at the population level allows studies of within host viral heterogeneity for patients with multiple infections, providing insights about viral evolutionary characteristics and responses to selective pressures. Resistance to antiviral treatment regimes are commonly observed in clinical cases with chronic infections. While escape from direct antiviral drugs can be explained by resistance mutations in targeted genomic regions, the absence of response to dual therapies has remained less understood.
In this study we implemented amplicon sequencing to survey genomic variation at the Core and NS5B regions of HCV over a period of 13 years for three patients followed for chronic hepatitis C at Grenoble-Alpes University Hospital. From samples obtained at different time points, we observed mixed infection by multiple genotypes in those patients. Genetic heterogeneity and sample composition analysis provided information about the changes in viral population over the course of clinical treatment, with NS5B experiencing a sharp increase in diversity after treatment initiation compared to baseline. Evidence for population structure was observed in all patients, occurring in divergent lineages in phylogenetic trees. These observations point towards diversifying selection occurring post-treatment, acting on standing genomic variation and maintaining high genetic heterogeneity during infection. Being associated with treatment efficiency, the results provide the first evidence for antiviral treatment inducing soft selective sweeps in chronically infected patients with multiple HCV genotypes.